PDF(Pubmed)
Abstract：
UNASSIGNED: Familial hypercholesterolaemia (FH) variant positive subjects have over double the cardiovascular risk of low-density-lipoprotein-cholesterol (LDL-C) matched controls. It is desirable to optimise FH variant detection.
UNASSIGNED: We identified 213 subjects with FH gene panel reports (LDLR, APOB, PCSK9, and APOE) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded. Demographic, clinical and lipid parameters were recorded.
UNASSIGNED: A 31/213 (14.6%) patients had pathogenic or likely pathogenic FH variants. 10/213 (4.7%) had variants of uncertain significance. Compared with patients without FH variants, patients with FH variants were younger (median age, 39 years vs. 48 years), had more tendon xanthomata (25.0% vs. 11.4%), greater proportion of first degree relatives with total cholesterol >95th percentile (40.6% vs. 16.5%), higher LDL-C (median, 271 mg/dL vs. 236 mg/dL), and lower triglycerides (median, 115 mg/dL vs. 159 mg/dL). The Besseling et al. model (c-statistic 0.798) improved FH variant discrimination over Friedewald LDL-C (c-statistic 0.724), however, Dutch Lipid Clinic Network Score (DLCNS) did not (c-statistic 0.665). Sampson LDL-C (c-statistic 0.734) had similar discrimination to Friedewald.
UNASSIGNED: Although tendon xanthomata and first degree relatives with high total cholesterol >95th percentile were associated with FH variants, DLCNS or Simon Broome criteria did not improve FH detection over LDL-C. Sampson LDL-C did not significantly improve discrimination over Friedewald. Although lower triglycerides and younger age of presentation are positively associated with presence of FH variants, this information is not commonly used in FH detection algorithms apart from Besseling et al.
UNASSIGNED: We identified 213 subjects with FH gene panel reports (LDLR, APOB, PCSK9, and APOE) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded. Demographic, clinical and lipid parameters were recorded.
UNASSIGNED: A 31/213 (14.6%) patients had pathogenic or likely pathogenic FH variants. 10/213 (4.7%) had variants of uncertain significance. Compared with patients without FH variants, patients with FH variants were younger (median age, 39 years vs. 48 years), had more tendon xanthomata (25.0% vs. 11.4%), greater proportion of first degree relatives with total cholesterol >95th percentile (40.6% vs. 16.5%), higher LDL-C (median, 271 mg/dL vs. 236 mg/dL), and lower triglycerides (median, 115 mg/dL vs. 159 mg/dL). The Besseling et al. model (c-statistic 0.798) improved FH variant discrimination over Friedewald LDL-C (c-statistic 0.724), however, Dutch Lipid Clinic Network Score (DLCNS) did not (c-statistic 0.665). Sampson LDL-C (c-statistic 0.734) had similar discrimination to Friedewald.
UNASSIGNED: Although tendon xanthomata and first degree relatives with high total cholesterol >95th percentile were associated with FH variants, DLCNS or Simon Broome criteria did not improve FH detection over LDL-C. Sampson LDL-C did not significantly improve discrimination over Friedewald. Although lower triglycerides and younger age of presentation are positively associated with presence of FH variants, this information is not commonly used in FH detection algorithms apart from Besseling et al.
摘要：
■家族性高胆固醇血症（FH）变异阳性受试者的低密度脂蛋白胆固醇（LDL-C）匹配对照的心血管风险增加了一倍以上。期望优化FH变体检测。
■我们确定了213名具有FH基因小组报告的受试者（LDLR，APOB,PCSK9和APOE)基于总胆固醇>310mg/dL；不包括>400mg/dL的甘油三酯，级联筛选，和未记录治疗前LDL-C的患者。人口统计,记录临床和血脂参数.
■A31/213（14.6%）患者有致病性或可能致病性FH变异。10/213(4.7%)具有不确定意义的变异。与没有FH变异的患者相比，有FH变异的患者更年轻(中位年龄，39年vs.48岁),有更多的肌腱黄瘤（25.0%vs.11.4%），总胆固醇>95百分位数的一级亲属比例更高(40.6%与16.5%），较高的LDL-C（中位数，271mg/dLvs.236毫克/分升)，和较低的甘油三酯(中位数，115mg/dLvs.159mg/dL)。贝塞林等人。模型(c-统计量0.798)改进了FH变异区分度优于FriedewaldLDL-C(c-统计量0.724)，然而,荷兰脂质临床网络评分（DLCNS）没有（c统计量0.665）。SampsonLDL-C（c统计量0.734）与Friedewald相似。
■尽管总胆固醇>95百分位数高的肌腱黄瘤和一级亲属与FH变异有关，DLCNS或SimonBroome标准并未改善LDL-C的FH检测。SampsonLDL-C并未显着改善对Friedewald的歧视。尽管较低的甘油三酯和较年轻的表现与FH变体的存在呈正相关，除了Besseling等人之外，这些信息在FH检测算法中并不常用。
■我们确定了213名具有FH基因小组报告的受试者（LDLR，APOB,PCSK9和APOE)基于总胆固醇>310mg/dL；不包括>400mg/dL的甘油三酯，级联筛选，和未记录治疗前LDL-C的患者。人口统计,记录临床和血脂参数.
■A31/213（14.6%）患者有致病性或可能致病性FH变异。10/213(4.7%)具有不确定意义的变异。与没有FH变异的患者相比，有FH变异的患者更年轻(中位年龄，39年vs.48岁),有更多的肌腱黄瘤（25.0%vs.11.4%），总胆固醇>95百分位数的一级亲属比例更高(40.6%与16.5%），较高的LDL-C（中位数，271mg/dLvs.236毫克/分升)，和较低的甘油三酯(中位数，115mg/dLvs.159mg/dL)。贝塞林等人。模型(c-统计量0.798)改进了FH变异区分度优于FriedewaldLDL-C(c-统计量0.724)，然而,荷兰脂质临床网络评分（DLCNS）没有（c统计量0.665）。SampsonLDL-C（c统计量0.734）与Friedewald相似。
■尽管总胆固醇>95百分位数高的肌腱黄瘤和一级亲属与FH变异有关，DLCNS或SimonBroome标准并未改善LDL-C的FH检测。SampsonLDL-C并未显着改善对Friedewald的歧视。尽管较低的甘油三酯和较年轻的表现与FH变体的存在呈正相关，除了Besseling等人之外，这些信息在FH检测算法中并不常用。
